This project seeks to investigate the nature of the cells of origin of acute childhood leukemias and the factors which govern their differentiation and proliferation. We plan to increasingly focus on the possibility that natural killer (NK) cells are committed pre-thymic T cell precursors which function as regulators in the hemopoietic system and as such mediate resistance to hemopoietic tumors. We will attempt to confirm that NK cells regulate EBV-induced B cell proliferation and examine by co-cultivation experiments the influence of various human T cell subpopulations on myelopoiesis and erythropoiesis. In addition we will attempt to determine the prognostic significance and therapeutic implications of all phenotypes defined by a panel of cell surface markers and to develop a mouse hybridoma which produces monoclonal antibody to human terminal transferase, an extremely useful leukemia cell marker.